Abstract

Maternal metabolism during pregnancy impacts the developing fetus, affecting offspring birth weight and adiposity. This has
important implications for metabolic health later in life (e.g., offspring of mothers with pre-existing or gestational diabetes
mellitus have an increased risk of metabolic disorders in childhood). To identify genetic loci associated with measures of
maternal metabolism obtained during an oral glucose tolerance test at ∼28 weeks’ gestation, we performed a genome-wide association
study of 4,437 pregnant mothers of European (n = 1,367), Thai (n = 1,178), Afro-Caribbean (n = 1,075), and Hispanic (n = 817) ancestry, along with replication of top signals in three additional European ancestry cohorts. In addition to identifying
associations with genes previously implicated with measures of glucose metabolism in nonpregnant populations, we identified
two novel genome-wide significant associations: 2-h plasma glucose and HKDC1, and fasting C-peptide and BACE2. These results suggest that the genetic architecture underlying glucose metabolism may differ, in part, in pregnancy.